Identifying cell receptors for the nanoparticle protein corona using genome screens. Ngo, W., Wu, J. L. Y., Lin, Z. P., Zhang, Y., Bussin, B., Granda Farias, A., Syed, A. M., Chan, K., Habsid, A., Moffat, J., & Chan, W. C. W. Nature Chemical Biology, Aug, 2022.
Identifying cell receptors for the nanoparticle protein corona using genome screens [link]Paper  doi  abstract   bibtex   30 downloads  
Nanotechnology provides platforms to deliver medical agents to specific cells. However, the nanoparticle's surface becomes covered with serum proteins in the blood after administration despite engineering efforts to protect it with targeting or blocking molecules. Here, we developed a strategy to identify the main interactions between nanoparticle-adsorbed proteins and a cell by integrating mass spectrometry with pooled genome screens and Search Tool for the Retrieval of Interacting Genes analysis. We found that the low-density lipoprotein (LDL) receptor was responsible for approximately 75% of serum-coated gold nanoparticle uptake in U-87 MG cells. Apolipoprotein B and complement C8 proteins on the nanoparticle mediated uptake through the LDL receptor. In vivo, nanoparticle accumulation correlated with LDL receptor expression in the organs of mice. A detailed understanding of how adsorbed serum proteins bind to cell receptors will lay the groundwork for controlling the delivery of nanoparticles at the molecular level to diseased tissues for therapeutic and diagnostic applications.
@Article{Ngo2022,
author={Ngo, Wayne
and Wu, Jamie L. Y.
and Lin, Zachary P.
and Zhang, Yuwei
and Bussin, Bram
and Granda Farias, Adrian
and Syed, Abdullah M.
and Chan, Katherine
and Habsid, Andrea
and Moffat, Jason
and Chan, Warren C. W.},
title={Identifying cell receptors for the nanoparticle protein corona using genome screens},
journal={Nature Chemical Biology},
year={2022},
month={Aug},
day={11},
abstract={Nanotechnology provides platforms to deliver medical agents to specific cells. However, the nanoparticle's surface becomes covered with serum proteins in the blood after administration despite engineering efforts to protect it with targeting or blocking molecules. Here, we developed a strategy to identify the main interactions between nanoparticle-adsorbed proteins and a cell by integrating mass spectrometry with pooled genome screens and Search Tool for the Retrieval of Interacting Genes analysis. We found that the low-density lipoprotein (LDL) receptor was responsible for approximately 75{\%} of serum-coated gold nanoparticle uptake in U-87 MG cells. Apolipoprotein B and complement C8 proteins on the nanoparticle mediated uptake through the LDL receptor. In vivo, nanoparticle accumulation correlated with LDL receptor expression in the organs of mice. A detailed understanding of how adsorbed serum proteins bind to cell receptors will lay the groundwork for controlling the delivery of nanoparticles at the molecular level to diseased tissues for therapeutic and diagnostic applications.},
issn={1552-4469},
doi={10.1038/s41589-022-01093-5},
url={https://doi.org/10.1038/s41589-022-01093-5}
}

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